Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Transforming the lecture-hall environment: The fully interactive physics lecture,

Numerous reports suggest that learning gains in introductory university physics courses may be increased by &apos;&apos;active-learning&apos;&apos; instructional methods. These methods engender greater mental engagement and more extensive student-student and student-instructor interaction than does a typical lecture class. It is particularly challenging to transfer these methodologies to the large-enrollment lecture hall. We report on seven years of development and testing of a variant of Peer Instruction as pioneered by Mazur that aims at achieving virtually continuous instructorstudent interaction through a &apos;&apos;fully interactive&apos;&apos; physics lecture. This method is most clearly distinguished by instructor-student dialogues that closely resemble one-on-one instruction. We present and analyze a detailed example of such classroom dialogues, and describe the format, procedures, and curricular materials required for creating the desired lecture-room environment. We also discuss a variety of assessment data that indicate strong gains in student learning, consistent with other researchers. We conclude that interactive-lecture methods in physics instruction are practical, effective, and amenable to widespread implementation

Use of In-class Physics Demonstrations in Highly Interactive Format

This paper, presented at the 2001 Physics Education Research Conference, demonstrates how traditional classroom demonstrations may be converted into active-learning experiences through linked multiple-choice question-and-answer sequences. Sample question sequences and worksheet materials are presented, as well as preliminary assessment data

Transforming the lecture-hall environment: The fully interactive physics lecture

Numerous reports suggest that learning gains in introductory university physics courses may be increased by “active-learning” instructional methods. These methods engender greater mental engagement and more extensive student–student and student–instructor interaction than does a typical lecture class. It is particularly challenging to transfer these methodologies to the large-enrollment lecture hall. We report on seven years of development and testing of a variant of Peer Instruction as pioneered by Mazur that aims at achieving virtually continuous instructor–student interaction through a “fully interactive” physics lecture. This method is most clearly distinguished by instructor–student dialogues that closely resemble one-on-one instruction. We present and analyze a detailed example of such classroom dialogues, and describe the format, procedures, and curricular materials required for creating the desired lecture-room environment. We also discuss a variety of assessment data that indicate strong gains in student learning, consistent with other researchers. We conclude that interactive-lecture methods in physics instruction are practical, effective, and amenable to widespread implementation

Ethanol Modulates BKCa Channels by Acting as an Adjuvant of Calcium

Ethanol modulation of calcium- and voltage-gated potassium (slo1) channels alters neuronal excitability, cerebrovascular tone, brain function, and behavior, yet the mechanism of this modulation remains unknown. Using patch-clamp electrophysiology on recombinant BKCa channels cloned from mouse brain and expressed in Xenopus laevis oocytes, we demonstrate that ethanol, even at concentrations maximally effective to modulate BKCa channel function (100 mM), fails to gate the channel in absence of activating calcium. Moreover, ethanol does not modify intrinsic, voltage- or physiological magnesium-driven gating. The alcohol works as an adjuvant of calcium by selectively facilitating calcium-driven gating. This facilitation, however, renders differential ethanol effects on channel activity: potentiation at low (\u3c10 μM) and inhibition at high (\u3e10 μM) calcium, this dual pattern remaining largely unmodified by coexpression of brain slo1 channels with the neuronally abundant BKCa channel β4 subunit. Calcium recognition by either of the slo1 high-affinity sensors (calcium bowl and RCK1 Asp362/Asp367) is required for ethanol to amplify channel activation by calcium. The Asp362/Asp367 site, however, is necessary and sufficient to sustain ethanol inhibition. This inhibition also results from ethanol facilitation of calcium action; in this case, ethanol favors channel dwelling in a calcium-driven, low-activity mode. The agonist-adjuvant mechanism that we advance from the calcium-ethanol interaction on slo1 might be applicable to data of ethanol action on a wide variety of ligand-gated channels

Modulatory effects of dextran sulfate and fucoidan on binding and channel properties of AMPA receptors isolated from rat brain

Previous work showed that the glycosaminoglycan (GAG) dextran sulfate (500 kDa) altered the binding and channel properties of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐type glutamate receptors. The current study compared the effects of dextran sulfate with another GAG, fucoidan (100–180 kDa), to determine whether GAG‐mediated changes in high‐affinity binding of AMPA receptors have a concomitant influence on specific channel properties. Dextran sulfate was more potent in inhibiting high‐affinity AMPA binding to solubilized receptors (EC50 of 7 nM) compared to fucoidan (EC50 of 124 nM). Similarly, dextran sulfate was more potent in modulating the channel properties of purified and reconstituted AMPA receptors. Dextran sulfate, at 1 μg/ml (2 nM), produced a three to fourfold increase in open channel probability and a threefold increase in mean burst duration of channel activity elicited by 283 nM AMPA. The mean open time was increased by two to threefold and closed times were decreased by two to eightfold. Fucoidan produced similar effects at a concentration many times higher than that of dextran sulfate. Dextran sulfate and fucoidan had no effect on the single channel conductance or the ability of a specific antagonist to block AMPA channels. The effects of GAGs on multichannel patches showed an interactive channel gating behavior resulting in macroscopic currents with long lived open channel life times. These findings suggest that GAG components of proteoglycans can interact with and alter the binding affinity of AMPA receptors and modulate their functional properties. Synapse 60:456–464, 2006. © 2006 Wiley‐Liss, Inc

Single Channel Recordings From Synaptosomal AMPA Receptors

Synaptic glutamate receptors play a prominent role in the excitatory neurotransmission in the vertebrate central nervous system. Although elucidation of the functional properties of glutamate receptors using electrophysiologic analyses has yielded important information, methodological and technological limitations have prevented direct measurement of single channel properties of synaptic receptors. Here, we have isolated murine mossy fiber synaptosomes and reconstituted them into small artificial lipid bilayers to characterize the single-channel properties of synaptic α amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-subtype glutamate receptors. The reconstituted synaptosomal receptors were activated by nanomolar concentrations of AMPA and blocked by a potent AMPA receptor antagonist. The synaptosomal AMPA receptors exhibited channel conductances of 14–56 pS and linear current-voltage relationship. The open and closed dwell time distributions of single channel currents were best described by three exponentials. These channels frequently exhibited burst behavior with long burst duration of approx 60 ms. Experiments with multichannel recordings revealed that steady state probabilities could not be fitted using a binomial distribution, indicating a cooperative channel gating behavior that would account for larger membrane currents. Our findings suggest that isolation, reconstitution into lipid bilayers, and subsequent single channel analysis of synaptosomal receptors is a useful method for investigation of synaptic AMPA receptors